Several human interleukin-2 (IL-2) mutant proteins have been produced previously by site-directed mutagenesis and found to have different capacities to induce T-cell proliferative activity, activate natural killer cells and to induce interferon-r production. The consistency of relative activities of the mutant proteins in these different assays indicate that a similar if not identical functional structure(s) is responsible for these biological activities. Receptor binding studies showed that the activities of most proteins correlated well with their respective affinities for high-affinity IL-2 receptors on CTLL2 cells. One of the mutant proteins wit deletion of cysteine 25 (des Cys 125) showed different affinity for CTLL-2 cells and MIA-144 cells. Since CTLL-2 cells express both p55 and p7O receptors while MIA-144 cells express mainly p7O receptor, these results suggest that binding of IL-2 or mutant proteins to IL2Rp7O receptor is essential for the induction of biological effects. We are continuing this study by producing more mutants to further elaborate our findings.